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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort
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Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort

机译：生命跨度延伸，减少病症信号：信号类型，性别和实验队列衰老效果的促进

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Reduced somatotrophic signaling through the growth hormone (GH) and insulin-like growth factor pathways (IGF1) can delay aging, although the degree of life-extension varies markedly across studies. By collating data from previous studies and using meta-analysis, we tested whether factors including sex, hormonal manipulation, body weight change and control baseline mortality quantitatively predict relative life-extension. Manipulations of GH signaling (including pituitary and direct GH deficiencies) generate significantly greater extension in median life span than IGF1 manipulations (including IGF1 production, reception, and bioactivity), producing a consistent shift in mortality risk of mutant mice. Reduced Insulin receptor substrate (IRS) expression produces more similar life-extension to reduced GH, although effects are more heterogeneous and appear to influence the demography of mortality differently. Life-extension with reduced IGF1 signaling, but neither GH nor IRS signaling, increases life span significantly more in females than males, and in cohorts where control survival is short. Our results thus suggest that reduced GH signaling has physiological benefits to survival outside of its actions on circulating IGF1. In addition to these biological moderators, we found an overrepresentation of small sample sized studies that report large improvements in survival, indicating potential publication bias. We discuss how this could potentially confound current conclusions from published work, and how this warrants further study replication.
机译：通过生长激素（GH）和胰岛素样生长因子途径（IGF1）降低了病症信号传导，但延迟老化，尽管寿命的程度显着变化。通过从先前研究和使用META分析的数据进行分析，我们测试了是否包括性行为，荷尔蒙操纵，体重变化和控制基线死亡的因素，定量预测相对寿命延伸。 GH信令（包括垂体和直接GH缺陷）的操纵在中位寿命跨度的延伸比IGF1操纵（包括IGF1生产，接收和生物活性）产生明显更大的延伸，从而产生突变小鼠的死亡风险的一致变化。减少的胰岛素受体衬底（IRS）表达产生更类似的寿命减少GH，但效果更为异质，并且似乎不同地影响死亡的人口统计。寿命扩展降低IGF1信号传导，但是GH也不是IRS信号传导，在女性的寿命比男性更高，并且在控制存活率短暂的群组中。因此，我们的结果表明，减少GH发信号传导在其对循环IGF1上的动作外生存的生理效果。除了这些生物主导者之外，我们还发现了对小型样本大小研究的过度陈述，报告存活率的大量改善，表明潜在的出版物偏见。我们讨论如何从发布的工作中可能会困扰当前的结论，以及如何进一步研究复制。

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